The Interaction of Liver Phosphorylase <em>a</em> with Glucose and AMP.

The effects of glucose and of AMP on several properties of purified dog liver phosphorylase a have been investigated. Glucose stimulated several-fold the conversion of phosphorylase a into b, catalyzed by purified phosphorylase phosphatase. The reaction was strongly inhibited by AMP in the absence of glucose, and much less in the presence of glucose. Conversely, the concentration of glucose that gave half-maximal stimulation was increased several-fold by the nucleotide. Similar effects were observed when the phosphorylase phosphatase was studied in crude liver preparations. 1,5-Anhydroglucitol, α-methylglucoside and 2-deoxyglucose, quoted in order of decreasing efficiency, also stimulated the phosphorylase phosphatase reaction. Similar results were obtained when the conversion of phosphorylase a into b′ by trypsin was studied. The effect of glucose on the kinetics of purified liver phosphorylase a was mostly to decrease affinity for glucose 1-phosphate and to increase cooperativity between glucose 1-phosphate binding sites. AMP had the opposite effect and each of the two ligands antagonized the binding of the other. Glucose derivatives, in the order of efficiency given above, mimicked the effects of glucose. Glucose and the same glucose analogues, as well as AMP, protected phosphorylase a against denaturation at 55 °C. These results indicate that the stimulation of the phosphorylase phosphatase reaction by glucose is secondary to the binding of the hexose to phosphorylase a, and that this binding is modulated by the concentration of AMP. The physiological implication of these findings is discussed. [ABSTRACT FROM AUTHOR]